ALBERT

Description: Background: Acute graft-versus-host disease (aGvHD) remains a critical barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nearly all patients who undergo allo-HSCT receive red blood cell (RBC) transfusions during the first 30 days post-transplant, but the long-term effects of transfusions on post-transplant outcomes remain unclear. Preclinical and clinical studies indicate that RBC transfusions can activate dendritic cells (DCs) sensitizing transplant recipients to minor histocompatibility antigens (miHA). Initial interactions between donor T cell and DC regulate donor T cell activation and proliferation. We hypothesized that RBC transfusion may contribute to aGvHD in allo-HSCT patients by activating DC and stimulating allo-reactive T cells or other inflammatory pathways. Methods: We conducted a retrospective study of 336 adult allo-HSCT patients at Emory University Hospital from 2007 to 2013. In cases involving multiple transplants, only data relevant to the first allo-HSCT was included. Graft sources were restricted to bone marrow and G-CSF mobilized peripheral blood (excluded cord blood and T cell depleted grafts). 181 patients (54%) were male and 155 (46%) were female. Patients received transplants from matched related donors (n=123, 37%) or matched unrelated donors (n=213, 63%) for treatment of AML (n=132), ALL (n=40), acute leukemia (n=5), MDS (n=41), CML (n=22), CLL (n=15), HD (n=6), NHL (n=33), AA (n=10), MM (n=7) or other diseases (n=25). aGvHD with onset of up to 150 days after allo-HSCT was the primary end-point. Leuko-reduced and irradiated RBC transfusions administered during the week prior to transplant and 30 days post-transplant (while patients were closely monitored at the transplant center) were provided by a single Blood Bank. The median follow up time was 14.6 months post transplantation (range, 0.3 to 65.1 months). The relationship of RBC transfusions to aGvHD was determined as a time-dependent variable or as a function of the total number of RBC units transfused. Results: 306 patients (91%) received RBC transfusions during the observation timeframe, while 30 (9%) did not require transfusion (median 6). 221 patients (66%) developed grade I-IV aGvHD with a distribution of 85 (25%), 72 (21%), 47 (14%), and 11 (3%) of patients with maximum grade of I, II, III and IV, respectively, while 115 (34%) patients did not show any signs of aGvHD. We compared transfusion history, prior to the diagnosis of GvHD, in patients who developed grade 0-II aGvHD (n=272, 81%) vs. grade III-IV aGvHD (n=64, 19%). Patients with grade III-IV aGvHD received more RBC units (median 8) than patients with grade 0-II aGvHD (median 4). In univariable Cox regression analysis, factors significantly associated with grade III-IV acute GvHD were HLA match (HR 2.22, p=0.004), number of RBC units per week (HR=1.26, p

Description: Introduction: Rituximab (R) administration results in depletion of blood B cells and suppression of B cell reconstitution for several months after, with suggestions that T cell reconstitution may also be impaired. We hypothesized that pre-transplant R would be associated with delayed B and T cell reconstitution after allo-HSCT compared with non-R-treated allo-HSCT recipients. Methods: We conducted a retrospective analysis of 360 patients who underwent allo-HSCT using BM or G-CSF mobilized PB. Recipients of cord blood, T cell depleted grafts and 2nd allo-HSCT were excluded. Analysis of lymphocyte subsets in at least one blood at 1, 3, 6, 12, and 24 months post-allo-HSCT was available for 255 eligible patients. Data on lymphocyte recovery was censored after DLI or post-transplant R therapy. Post-HSCT lymphocyte recovery in 217 patients who never received R (no-R) was compared to 38 patients who had received R before allo-HSCT (+R) including 12 CLL, 19 NHL, and 7 B-cell ALL patients. +R patients received a median of 9 doses of R with the last dose of R at a median of 45 days pre-transplant. Results: Mean lymphocyte numbers in the blood at 1, 3, 6, 12, and 24 months were B-cells: 55 ± 465/µL, 82 ± 159/µL, 150 ± 243/µL, 255 ± 345/µL, and 384 ± 369/µL (normal range 79-835); and T-cells: 65 ± 987/µL, 831 ± 667/µL, 1058 ± 788/µL, 1291 ± 985/µL, and 1477 ± 1222/µL (normal range 675-3085). Lymphocyte reconstitution kinetics did not vary significantly based upon the intensity of the conditioning regimen or related vs. unrelated donors allowing aggregation of patients in the +R and no-R groups (Figure). B cell reconstitution in the +R patients was higher at 1 month post-allo-HSCT (relative value of 143% p=0.008) and lower at 3 months post-transplant (19.2%, p=0.069) compared to no-R patients. Blood B cells in the +R group rebounded by the 6th month post-allo-HSCT and remained higher than the no-R group through the 24th month post-HSCT (197% at the 6th month, p=0.037). Higher levels of B-cells at 1 month in the +R group was due to higher blood B-cells at 1 month post-HSCT among 12 CLL patients compared with no-R patients (423%, p